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TR34/L98H Aspergillus Resistance — SCE Infectious Diseases MCQ

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HardFungal InfectionsTR34/L98H Aspergillus ResistanceSCE Infectious Diseases

A 55-year-old woman develops Aspergillus fumigatus invasive aspergillosis while on Itraconazole prophylaxis. Antifungal susceptibility testing (EUCAST methodology) shows: Itraconazole MIC >16 mg/L, Voriconazole MIC 4 mg/L (resistant), Posaconazole MIC 0.5 mg/L (resistant). These results suggest a specific resistance mechanism. What is it?

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Correct answer: B — TR34/L98H mutation in the CYP51A gene — the most common pan-azole environmental resistance mechanism in A. fumigatus, driven by agricultural azole fungicide use

The combination of elevated MICs to Itraconazole, Voriconazole, AND Posaconazole suggests a multi-azole resistance mechanism. TR34/L98H is the most common: a tandem repeat in the CYP51A promoter (causing overexpression) combined with an amino acid substitution (reducing azole binding). This mutation arises environmentally (selected by agricultural triazole fungicides in soil) and is acquired by patients who inhale resistant spores — hence resistance is present at first isolation without prior patient azole exposure. Treatment requires non-azole agents: Liposomal Amphotericin B first-line.

Reference: BSAC 2024 – Azole resistance in Aspergillus; ECMM/ISHAM 2024